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MicroRNA-126 accelerates IgE-mediated mast cell degranulation associated with the PI3K/Akt signaling pathway by
Yuan Bao1, Song Wang2, Yang Gao2
1Department of Network Medicine, The Central Hospital of Wuhan, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430014, P.R. China.
Abstract:
Mast cells (MCs) have been reported to serve a crucial role in allergic diseases, including asthma, allergic rhinitis and anaphylaxis. A previous study revealed that microRNA-126 (miR-126) was associated with airway hyperresponsiveness induced by house dust mites, however the molecular mechanisms were unclear. The present study aimed to investigate the effect of miR-126 on immunoglobulin E (IgE)-regulated MC degranulation and explore its underlying mechanisms. miR-126 expression was quantified using a rat model in vivo and in rat peritoneal mast cells (RPMCs) in vitro. Overexpression or downregulation of miR-126 was established by transfection with miR-126 mimics or miR-126 inhibitors and MC degranulation was subsequently evaluated. The effect of miR-126 on protein kinase B (Akt) and phosphorylated Akt protein expression was examined by western blot analysis. The phosphoinositide 3-kinase (PI3K) inhibitor (LY294002) was used to determine the role of the PI3K/Akt signaling pathway. In addition, cytosolic calcium (Ca2+) levels were measured by a fura-2 assay. The results demonstrated that miR-126 expression was upregulated in the ear tissues of rats with allergic contact dermatitis and IgE-activated MCs. The overexpression of miR-126 in RPMCs was established following miR-126 mimic transfection. The release of β-hexosaminidase and histamine, markers of MC degranulation, were significantly increased in cells with miR-126 overexpression. The phosphorylation of Akt was significantly increased following transfection with miR-126 mimics in stimulated cells, however the signaling activation was abrogated by LY294002. In addition, Ca2+ influx was significantly promoted in stimulated RPMCs overexpressing miR-126. These results indicate that miR-126 accelerated IgE-mediated MC degranulation associated with the PI3K/Akt signaling pathway by promoting Ca2+ influx. This suggests that miR-126 may be a promising therapeutic target for the treatment of allergic skin diseases.
Insights
MicroRNA-126 (miR-126) accelerates immunoglobulin E (IgE)-mediated mast cell degranulation by activating the PI3K/Akt pathway and increasing calcium influx. This finding suggests miR-126 as a potential therapeutic target for allergic skin diseases.
Area of Science:
- Immunology
- Molecular Biology
- Dermatology
Background:
- Mast cells (MCs) are key players in allergic reactions like asthma and anaphylaxis.
- MicroRNA-126 (miR-126) is implicated in airway hyperresponsiveness, but its role in MC degranulation is unclear.
- Understanding miR-126's function in MCs is crucial for developing targeted allergy therapies.
Purpose of the Study:
- To investigate the impact of miR-126 on immunoglobulin E (IgE)-mediated mast cell degranulation.
- To elucidate the molecular mechanisms underlying miR-126's effect on mast cell activation.
- To explore miR-126 as a potential therapeutic target for allergic skin diseases.
Main Methods:
- Quantified miR-126 expression in a rat model of allergic contact dermatitis and in rat peritoneal mast cells (RPMCs).
- Manipulated miR-126 levels using mimics and inhibitors in RPMCs, assessing degranulation markers (β-hexosaminidase, histamine).
- Analyzed the PI3K/Akt signaling pathway via Western blot and used a PI3K inhibitor (LY294002); measured intracellular calcium (Ca2+) levels using fura-2 assay.
Main Results:
- miR-126 expression was elevated in allergic skin tissues and IgE-activated MCs.
- Overexpression of miR-126 in RPMCs significantly enhanced the release of β-hexosaminidase and histamine.
- miR-126 overexpression promoted Akt phosphorylation and Ca2+ influx, effects mediated by the PI3K/Akt pathway.
Conclusions:
- miR-126 promotes IgE-mediated mast cell degranulation.
- The mechanism involves the PI3K/Akt signaling pathway and increased Ca2+ influx.
- miR-126 represents a promising therapeutic target for allergic skin conditions.
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